Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis.

Journal Article (Journal Article)

AIMS: Inorganic nitrate and nitrite from endogenous and dietary sources have emerged as alternative substrates for nitric oxide (NO) formation in addition to the classic L-arginine NO synthase (NOS)-dependent pathway. Here, we investigated a potential cross-talk between these two pathways in the regulation of vascular function. RESULTS: Long-term dietary supplementation with sodium nitrate (0.1 and 1 mmol kg(-1) day(-1)) in rats caused a reversible dose-dependent reduction in phosphorylated endothelial NOS (eNOS) (Ser1177) in aorta and a concomitant increase in phosphorylation at Thr495. Moreover, eNOS-dependent vascular responses were attenuated in vessels harvested from nitrate-treated mice or when nitrite was acutely added to control vessels. The citrulline-to-arginine ratio in plasma, as a measure of eNOS activity, was reduced in nitrate-treated rodents. Telemetry measurements revealed that a low dietary nitrate dose reduced blood pressure, whereas a higher dose was associated with a paradoxical elevation. Finally, plasma cyclic guanosine monophosphate increased in mice that were treated with a low dietary nitrate dose and decreased with a higher dose. INNOVATION AND CONCLUSIONS: These results demonstrate the existence of a cross-talk between the nitrate-nitrite-NO pathway and the NOS-dependent pathway in control of vascular NO homeostasis.

Full Text

Duke Authors

Cited Authors

  • Carlström, M; Liu, M; Yang, T; Zollbrecht, C; Huang, L; Peleli, M; Borniquel, S; Kishikawa, H; Hezel, M; Persson, AEG; Weitzberg, E; Lundberg, JO

Published Date

  • August 1, 2015

Published In

Volume / Issue

  • 23 / 4

Start / End Page

  • 295 - 306

PubMed ID

  • 24224525

Pubmed Central ID

  • PMC4523008

Electronic International Standard Serial Number (EISSN)

  • 1557-7716

Digital Object Identifier (DOI)

  • 10.1089/ars.2013.5481


  • eng

Conference Location

  • United States